Bromodeoxyuridme (BrdU) is a thymidine analogue capable of inducing epitheloid morphology and altering the expression of neuroendocrine markers in SCLC cell lines. The ability of BrdU to alter differentiation in neuronal, muscle and haematopoietic lineages has been well documented in the literature. Evidence suggests that this incorporation into the DNA alters the DNA’s conformation, which in turn may affect mteractions with specific transcription factors, leading to either inhibition or induction of differentiation. Following on from work previously performed in our laboratory, several pyrimidine analogues were studied to investigate if they possessed similar differentiating properties to BrdU. The DLKP cell line was established at the NICB from a tumour histologically diagnosed as a poorly differentiated lung carcinoma DLKP cells have properties which suggest they could be classified as either SLCL-V or non-small-cell-lung carcinoma with neuroendocrine differentiation (NSCLC-NE). In this study it demonstrate that the DLKP cell line, and the more differentiated adenocarcinoma line, A549, upon treatment with the BrdU and a panel of other pyrimidine analogues, showed increased expression of cytokeratms 8, 18 and 19 proteins. Increased protein expression levels of mtegnn subunits ct2 and Pi, as well as the cellular adhesion molecule Ep-CAM, was demonstrated in both cell lines following exposure to drug. DNA microarray experiments were also performed on DLKP cells exposed to BrdU, IdU and 5,2 -FdU Following gene expression analysis on these microarray experiments, lists of differentially expressed genes were generated. From earlier work performed in this thesis, we demonstrate that all three pyrimidine analogues induce a similar pattern of differentiation in DLKP cells. Therefore, the three microarray experiments were compared to each other in order to identify a common differentiation pathway We reveal that a total of 93 up-regulated genes were common to all three microarray expenments EASE analysis was performed on these 93 genes and identified 20 genes from this list of 93, which are thought to be involved in cellular development. From this list of 20 development genes, we identify in particular, two families of transcription factors that potentially are involved in the regulation of differentiation in our system. These transcription factor families are the Id and KLF proteins. We propose that the Id family of proteins in play an important part in the regulation of differentiation in pynmidine-treated DLKP cells. We also suggest a role for KLF4 in the regulation of cytokeratin expression, mediated through IFNy and STAT-1 proteins. The transcription factor YY1 is a 65kDa protein that is ubiquitously expressed and is highly conserved among human, mouse and Xenopus YY1 possesses the unusual property of regulating transcription in three ways, depending on the cellular context YY1 has been shown to activate, repress or initiate transcription of a number of cellular genes and has previously been shown to associate with cmyc, resulting in its activation and up-regulation. We have also shown that BrdU-treated cells show increased levels of c-Myc and eIF-4E protein. In order to investigate the role c-Myc and eIF-4E play in the differentiation of the DLKP lung cell line, a clonal variant of DLKP, DLKP-SQ, was transiently and stably transfected with a human YY1 cDNA expression vector. It was observed that in stable clones over-expression of YY1 upregulated c-Myc protein levels. The over-expression of YY1 appears to have further effects on other cellular genes such as increased levels of eIF-4E, eIF-2a and Ornithine Decarboxylase proteins. We also demonstrate that the transient over-expression of YY1 is capable of inducing genes identified as differentially expressed, namely Id2, Id3, HMOX1 and FHL1, in the DLKP, IdU and 5,2 -FdU microarray experiments.